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Fish oils rank among the world's most popular nutritional supplements and are purported to have numerous health benefits. Previous work suggested that fish oils increase collagen production; however, the effect of fish oils on musculoskeletal health is poorly understood. Further, the divergent effects of omega-3 (Ω3FA) and saturated fatty acids (SFA) remains poorly understood. We tested the effects of Ω3FA and SFAs on in vitro-engineered human ligament (EHL) function. EHLs were treated with bovine serum albumin (BSA)-conjugated eicosapentaenoic acid (EPA, 20:5(n-3)), palmitic acid (PA, 16:0), or a BSA control for 6 days. EPA did not significantly alter, whereas PA significantly decreased EHL function and collagen content. To determine whether this was an in vitro artifact, mice were fed a control or high-lard diet for 14 weeks and musculoskeletal mass, insulin sensitivity, and the collagen content, and mechanics of tendon and bone were determined. Body weight was 40 % higher on a HFD, but muscle, tendon, and bone mass did not keep up with body weight resulting in relative losses in muscle mass, tendon, and bone collagen, as well as mechanical properties. Importantly, we show that PA acutely decreases collagen synthesis in vitro to a similar extent as the decrease in collagen content with chronic treatment. These data suggest that Ω3FAs have a limited effect on EHLs, whereas SFA exert a negative effect on collagen synthesis resulting in smaller and weaker musculoskeletal tissues both in vitro and in vivo.

This article delves into why the United States and Singapore, despite their shared colonial history, democratic institutions, wealth, and global influence, have drastically different free speech models. This paper will look at three points of comparison: historical context, political theory, and evolution of judicial interpretation. By comparing the current events and the prevalent political theories at the time of drafting the Singaporean and American constitutions, this paper seeks to understand why the nations ratified contrasting free speech clauses.  However, the Constitution is only as meaningful as the courts interpret it, so this paper also explores how the respective Supreme Courts of Singapore and America have evolved their interpretation of the Constitution to shape their contrasting free speech models. While this paper will not argue which model of free speech is more effective, it will outline the underlying reasons for Singapore and America's drastically different free speech models.

Abstract Breast cancer is the most common malignancy affecting women worldwide and is notable for its morphologic and biologic diversity, with varying risks of recurrence following treatment. The Oncotype DX Breast Recurrence Score test is an important predictive and prognostic genomic assay for estrogen receptor positive/HER2 negative breast cancer that guides therapeutic strategies; however, such tests can be expensive, delay care, and are not widely available. The aim of this study was to develop a multi-model approach integrating the analysis of whole-slide images and clinicopathologic data to predict their associated breast cancer recurrence risks and categorize these patients into two risk groups according to the predicted score: low-risk and high-risk. The proposed novel methodology uses convolutional neural networks for feature extraction and vision transformers for contextual aggregation, complemented by a logistic regression model that analyzes clinicopathologic data for classification into two risk categories. This method was trained and tested on 956 hematoxylin and eosin-stained whole-slide images of 950 ER+/HER2− breast cancer patients with corresponding clinicopathological features that had prior Oncotype DX testing. The model’s performance was evaluated using an internal test set of 192 patients from Dartmouth Health and an external test set of 405 patients from the University of Chicago. The multi-model approach achieved an AUC of 0.91 (95% CI: 0.87–0.95) on the internal set and an AUC of 0.84 (95% CI: 0.78–0.89) on the external cohort for predicting low- and high-breast cancer recurrence risk categories based on the Oncotype DX recurrence score. With further validation, the proposed methodology could provide an alternative to assist clinicians in personalizing treatment for breast cancer patients and potentially improving their outcomes.

Mathematical learning has an important role and is often prioritized in education. In K-16 education, algebra is one of the most vital mathematical content domains: it represents one of the top barriers for students pursuing a postsecondary education. Game-based learning has been effective in fostering classroom math learning environments that are collaborative and focused on conceptual understanding. Sandbox games provide open-ended learning environments where players can set their own goals and level of effort. As part of the project "Math Snacks," the team designed Agrinautica, a sandbox game to enable constructivist-informed early algebra learning. This article identifies design recommendations for creating meaningful sandbox games for learning, considering students' and teachers' needs. Researchers discuss the decisions to create a sandbox game and describe challenges inherent in math learning through sandbox-type gameplay. This study provides impact results from a large-scale study of users of the game, and shares recommendations for developing future sandbox learning games.

Language learning classrooms are sites of discovery not only of language, but of identity, culture, and community. The pedagogical approach described here, critical media work (CMW), integrates language teaching and social issues by using media literacy as a bridge. CMW explores antiracist discourse in popular media (digital and analog) to dismantle simplified, binary thinking about race. CMW encourages semiotic analyses of antiracist discourse and examines messages along continuums that emphasize complexities and intersections of race, language, and culture. We share how language teachers at two urban colleges that serve immigrant populations integrate CMW into their classes, and we discuss the effectiveness of this pedagogy in terms of language learning and antiracist education. We maintain that language teaching and social justice education can support each other and that media literacy provides a meaningful and effective foundation for engaged antiracist pedagogy.

For teachers to provide students with meaningful instruction in area measurement, teachers need robust understandings of area. Here, I describe two cycles of a "lesson experiment" used to investigate prospective teachers' understandings of area units in an undergraduate mathematics class. For each cycle, I collected and analyzed the prospective teachers' written work and videotaped class discussions. The first cycle yielded a learning trajectory for helping prospective teachers better understand area units, which led to more teachers attaining the lesson goals in the second cycle. The paper articulates these classroom lessons and the lesson experiment process for fellow mathematics instructors and teacher educators.

BackgroundSchistosomiasis, a chronic parasitic disease, remains a public health issue in tropical and subtropical regions, especially in low and moderate-income countries lacking assured access to safe water and proper sanitation. A national prevalence survey carried out by the Brazilian Ministry of Health from 2011 to 2015 found a decrease in human infection rates to 1%, with 19 out of 26 states still classified as endemic areas. There is a risk of schistosomiasis reemerging as a public health concern in low-endemic regions. This study proposes an integrated landscape-based approach to aid surveillance and control strategies for schistosomiasis in low-endemic areas.Methodology/principal findingsIn the Middle Paranapanema river basin, specific landscapes linked to schistosomiasis were identified using a comprehensive methodology. This approach merged remote sensing, environmental, socioeconomic, epidemiological, and malacological data. A team of experts identified ten distinct landscape categories associated with varying levels of schistosomiasis transmission potential. These categories were used to train a supervised classification machine learning algorithm, resulting in a 92.5% overall accuracy and a 6.5% classification error. Evaluation revealed that 74.6% of collected snails from water collections in five key municipalities within the basin belonged to landscape types with higher potential for S. mansoni infection. Landscape connectivity metrics were also analysed.Conclusions/significanceThis study highlights the role of integrated landscape-based analyses in informing strategies for eliminating schistosomiasis. The methodology has produced new schistosomiasis risk maps covering the entire basin. The region's low endemicity can be partly explained by the limited connectivity among grouped landscape-units more prone to triggering schistosomiasis transmission. Nevertheless, changes in social, economic, and environmental landscapes, especially those linked to the rising pace of incomplete urbanization processes in the region, have the potential to increase risk of schistosomiasis transmission. This study will help target interventions to bring the region closer to schistosomiasis elimination.

ABSTRACT Introduction Head and neck cancer (HNC) is a significant global health burden, with late presentation leading to complex treatment. While human papillomavirus (HPV) infection has been implicated in HNC, data from low‐ and middle‐income countries (LMICs) are limited. In this study, we investigated the prevalence and role of HPV in head and neck cancers diagnosed in Rwanda. Methods A retrospective cross‐sectional study was conducted using Rwanda Cancer Registry from January 2011 through December 2020. p16 immunohistochemistry as a surrogate for HPV was performed on a randomly selected case. p16‐positive cases were genotyped. Results A total of 1001 patients with HNC were identified; 82% (n = 819) had squamous cell carcinoma. The mean age at diagnosis was 51.1 years, with a majority being males (58%). Oral cavity and lip (27%) were the most common primary cancer sites. Stage was unknown in most cases (75%, n = 747). HIV status was known in 33% (n = 334) of patients with 10% (n = 33) HIV‐positive; 22% of 202 randomly selected cases were p16‐positive; 34% of the p16‐positive cases were oropharynx. PCR analysis of p16‐positive cases showed 19% HPV positivity, and HPV16 was the most common high‐risk HPV strain, and 55.5% were recorded HPV‐positive by PCR. Conclusions HNC cases in Rwanda have been increasing from 2011 to 2020, with a significant portion being HPV‐positive. Strategies to implement routine testing for p16, especially in oropharynx cancer patients, improved preservation of tissue samples, collection of comprehensive information including cancer risk factors, staging, and treatment are needed in Rwanda.

The school food environment is a key intervention point for influencing children’s and adolescents’ diets. As more countries establish school meal programs to provide critical nourishment to students, establishing standards for the foods served can increase the consumption of key nutrients and limit the consumption of foods that do not build health. This global scoping review explores the prevalence and basic characteristics of national policies that regulate food served through school meals across 193 countries, particularly by restricting the provision of categories, nutrients, or ingredients of nutritional concern. We gathered evidence from policy databases, grey literature, peer-reviewed literature, and primary policy documents. We included nationally mandated policies that included restrictions on categories, nutrients, or ingredients of concern served in school meals. Policies that were sub-national, voluntary, and/or did not include restrictive language were excluded from this review. Data was collected in research electronic data capture then extracted into Microsoft Excel and analyzed for policy frequency, prevalence by world region or country income group, and prevalence of certain policy characteristics. Globally, only 15% of countries were found to have a national-level policy restricting foods served through school meals in some capacity, including either nutritional or categorical restrictions. The majority of these policies were found in high-income countries, and no low-income countries had a policy meeting inclusion criteria. Policies in Latin-American and Caribbean countries limited the content of more nutrients of concern than in other regions. Although many policies included explicit guidelines to monitor implementation, few outlined mechanisms for policy enforcement. Future research should evaluate the impact of various school meal regulatory approaches, including implementation of similar policies at sub-national levels, and other elements that affect the impact of school meal programs, such as procurement, infrastructure, costs to school and to students and their families, and acceptability and consumption of foods provided.

Abstract Schistosomiasis is a neglected tropical disease caused by Schistosoma parasites. Schistosoma are obligate parasites of freshwater Biomphalaria and Bulinus snails, thus controlling snail populations is critical to reducing transmission risk. As snails are sensitive to environmental conditions, we expect their distribution is significantly impacted by global change. Here, we used machine learning, remote sensing, and 30 years of snail occurrence records to map the historical and current distribution of forward-transmitting Biomphalaria hosts throughout Brazil. We identified key features influencing the distribution of suitable habitat and determined how Biomphalaria habitat has changed with climate and urbanization over the last three decades. Our models show that climate change has driven broad shifts in snail host range, whereas expansion of urban and peri-urban areas has driven localized increases in habitat suitability. Elucidating change in Biomphalaria distribution—while accounting for non-linearities that are difficult to detect from local case studies—can help inform schistosomiasis control strategies.

The cationic lipid 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) is one of the original synthetic cationic lipids used for the liposomal transfection of oligonucleotides in gene therapy. The key structural element of DOTAP is its quaternary ammonium headgroup that is responsible for interactions with both nucleic acids and target cell membranes. Because these interactions are fundamental to the design of a major class of transfection lipids, it is important to understand the structure of DOTAP and how it interacts with halide counterions. Here, we use x-ray and neutron diffraction techniques to examine the structure of DOTAP and how chloride (Cl-) and iodide (I-) counterions alter the hydration properties of the DOTAP headgroup. A problem of particular interest is the poor solubility of DOTAP/I- in water solutions. Our results show that the poor solubility results from very tight binding of the I- counterion to the headgroup and the consequent expulsion of water. The structural principles we report here are important for assessing the suitability of DOTAP and its quaternary ammonium derivatives for transfection.

Introduction: Despite the wide availability of clinical decision rules for imaging of the cervical spine after a traumatic injury (eg, NEXUS C-spine rule and Canadian C-spine rule), there is significant overutilization of computed tomography (CT) imaging in patients who are deemed to be at low risk for a clinically significant cervical spine injury by these clinical decision rules. The purpose of this study was to identify the major factors associated with the overuse of CT cervical spine imaging using a logistic regression model.Methods: This was a retrospective review of all adult patients who underwent CT cervical spine imaging for evaluation of a traumatic injury at a tertiary academic emergency department (ED) and three affiliate community EDs in January and February 2019. We performed multivariable logistic regression to identify factors associated with obtaining CT cervical spine imaging despite low-risk classification by the NEXUS C-spine Rule.Results: A total of 1,051 patients underwent CT cervical spine imaging for traumatic indications during the study period, and 889 patients were included in the analysis. Of these patients, 376 (42.3%) were negative by the NEXUS C-spine rule. Variables that were associated with increased likelihood of unnecessary imaging included age over 65, Emergency Severity Index (ESI) score 2 and 3, arrival as a walk-in, and anticoagulation status. Patients who presented to the tertiary academic ED had a significantly lower likelihood of unnecessary imaging. Twenty-one patients (2.4%) were found to have cervical spine fractures on imaging, two of whom were negative by the NEXUS C-spine rule, but neither had a clinically significant fracture.Conclusion: Cervical spine imaging is vastly overused in patients presenting to the ED with traumatic injuries, as adjudicated using the NEXUS C-spine rule as a reference standard. Older age, ESI level, arrival as a walk-in, and taking anticoagulation drugs were associated with overutilization of CT imaging. Conversely, presenting to the tertiary academic ED was associated with a lower likelihood of undergoing unnecessary imaging. This model can guide future interventions to optimize ED CT utilization and minimize unnecessary testing.

Social cognition is shaped by cultural and social-psychological contexts. Depending on the social cues displayed, the cognitive processes that emerge during embodied social interactions can vary. This study explored the influence of gender diverse social cues on interpersonal coordination and decision-making during dyadic interaction in virtual reality. Participants embodied either a transgender or cisgender avatar and interacted with a transgender confederate (human-controlled virtual agent). Results suggest that transgender embodied women and men displayed more interpersonal affiliation, via their coordination dynamics with the confederate, after an explicit gender identity disclosure. Additionally, cognitive flexibility for ambiguous decisions was influenced by attributions of responsibility made toward the confederate. However, cisgender embodied men did not substantially change their decision-making behaviours or increase their coordination with the confederate. Viscerally taking on the perspective and appearance of a transgender person, achieved through virtual embodiment and interaction, may support positive interactions between cisgender and transgender communities.

Fish oils rank among the world’s most popular nutritional supplements and are purported to have numerous health benefits. Previous work suggested that fish oils increase collagen production; however, the effect of fish oils on musculoskeletal health is poorly understood. Further, the divergent effects of omega-3 (Ω3FA) and saturated fatty acids (SFA) remains poorly understood. We tested the effects of Ω3FA and SFAs on in vitro-engineered human ligament (EHL) function. EHLs were treated with bovine serum albumin (BSA)-conjugated eicosapentaenoic acid (EPA, 20:5(n-3)), palmitic acid (PA, 16:0), or a BSA control for 6 days. EPA did not significantly alter, whereas PA significantly decreased EHL function and collagen content. To determine whether this was an in vitro artifact, mice were fed a control or high-lard diet for 14 weeks and musculoskeletal mass, insulin sensitivity, and the collagen content, and mechanics of tendon and bone were determined. Body weight was 40 % higher on a HFD, but muscle, tendon, and bone mass did not keep up with body weight resulting in relative losses in muscle mass, tendon, and bone collagen, as well as mechanical properties. Importantly, we show that PA acutely decreases collagen synthesis in vitro to a similar extent as the decrease in collagen content with chronic treatment. These data suggest that Ω3FAs have a limited effect on EHLs, whereas SFA exert a negative effect on collagen synthesis resulting in smaller and weaker musculoskeletal tissues both in vitro and in vivo.

Background and purpose: Daily target re-delineation in online adaptive radiotherapy (oART) introduces uncertainty. The aim of this study was to evaluate artificial intelligence (AI) generated contours and inter-observer target variation among radiotherapy technicians in cone-beam CT (CBCT) guided oART of bladder cancer. Materials and methods: For each of 10 consecutive patients treated with oART for bladder cancer, one CBCT was randomly selected and retrospectively included. The bladder (CTV-T) was AI-segmented (CTV-TAI). Seven radiotherapy technicians independently reviewed and edited CTV-TAI, generating CTV-TADP. Contours were benchmarked against a ground truth contour (CTV-TGT) delineated blindly from scratch. CTV-TADP and CTV-TAI were compared to CTV-TGT using volume, dice similarity coefficient, and bidirectional local distance. Dose coverage (D99%>95 %) of CTV-TGT was evaluated for treatment plans optimized for CTV-TAI and CTV-TADP with clinical margins. Inter-observer variation among CTV-TADP was assessed using coefficient of variation and generalized conformity index. Results: CTV-TGT ranged from 48.7 cm3 to 211.6 cm3. The median [range] volume difference was 4.5 [−17.8, 42.4] cm3 for CTV-TADP and −15.5 [−54.2, 4.3] cm3 for CTV-TAI, compared to CTV-TGT. Corresponding dice similarity coefficients were 0.87 [0.71, 0.95] and 0.84 [0.64, 0.95]. CTV-TGT was adequately covered in 68/70 plans optimized on CTV-TADP and in 6/10 plans optimized on CTV-TAI with clinical margins. The median [range] coefficient of variation was 0.08 [0.05, 0.11] and generalized conformity index was 0.78 [0.71, 0.88] among CTV-TADP. Conclusions: Target re-delineation in CBCT-guided oART of bladder cancer demonstrated non-isotropic inter-observer variation. Manual adjustment of AI-generated contours was necessary to cover ground truth targets.

Abstract Habitability at the surface of a planet depends on having an atmosphere long enough for life to develop. The loss of atmosphere to space is an important component in assessing planetary surface habitability. Current models of atmospheric escape from exoplanets are not well constrained by observations. Atmospheric escape observations from the terrestrial planets are available in public data archives. We recast oxygen escape rates from Earth derived from an instrument on Dynamics Explorer‐1 as function of solar wind and compare them to similar data from Mars. Analysis demonstrates that oxygen escape rates from Mars are not as sensitive to variations in solar power components as those from Earth. Available data from Venus can confirm or refute the assertion that oxygen escape from magnetized planets is more sensitive than that from unmagnetized planets.

The world of online learning has exploded over the past 15 years, causing professors to quickly determine the best methods for teaching in an online format. At this point there is much knowledge and experience to be explored to help inform both faculty and academic institutions. The purpose of this empirical research study was to seek additional knowledge from successful faculty members on the teaching strategies that contribute to student success in an online CACREP counselor education program. A discussion of previous research is provided with a focus on the best practices for teaching students in an online format. Secondly, the results from a faculty survey and faculty focus group are provided along with descriptions of helpful strategies for teaching online students. The findings indicate that empathic faculty engagement with students was a strong predictor of success. Another key factor was prompt constructive feedback along with intentionality in looking for ways to help students succeed. Overall, finding ways to connect with students personally increased retention rates as well as provided overall faculty and student satisfaction. A discussion follows with implications as well as suggestions for future research.

This paper describes a critical media analysis of antiracist messages from both teaching and research perspectives. Antiracist discourse of public media (yard signs and websites) was collected in two communities in the Northeastern United States in 2020 and are discussed here, first as a site of social construction of antiracism, and second as a model for pedagogy. As a critical media analysis, this study reveals antiracist messages on continuums from passive to active, low-risk to high risk, self-oriented to other-oriented, and detached "not racist" postures to actively antiracist stances. These continuums encourage interrogation of what it means to be antiracist as an individual and as a community. As a model for pedagogy, this study provides a flexible yet structured activity that asks students to observe messages where they live, interrogate the complexities of antiracism within their communities, and reflect on their own participation in antiracist work.

In this paper, we argue that Indigenous data sovereignty (IDS) is vital for addressing threats to ecosystems, as well as for Indigenous Peoples re-establishing and maintaining sovereignty over their territories. Indigenous knowledge-holders face pressure from non-Indigenous scientists to collaborate to address environmental problems, while the open data movement is pressuring them to make their data public. We examine the role of IDS in the context of cumulative effects and climate change that threaten salmon-bearing ecosystems in British Columbia, guided by content from an online workshop in June 2022 and attended exclusively by a Tier-1 audience (First Nations knowledge-holders and/or technical staff working for Nations). Attention to data is required for fruitful collaborations between Indigenous communities and non-Indigenous researchers to address the impacts of climate change and the cumulative effects affecting salmon-bearing watersheds in BC. In addition, we provide steps that Indigenous governments can take to assert sovereignty over data, recommendations that external researchers can use to ensure they respect IDS, and questions that external researchers and Indigenous partners can discuss to guide decision-making about data management. Finally, we reflect on what we learned during the process of co-creating materials.

Nanothermodynamics provides the theoretical foundation for understanding stable distributions of statistically independent subsystems inside larger systems. In this review, it is emphasized that extending ideas from nanothermodynamics to simplistic models improves agreement with the measured properties of many materials. Examples include non-classical critical scaling near ferromagnetic transitions, thermal and dynamic behavior near liquid–glass transitions, and the 1/f-like noise in metal films and qubits. A key feature in several models is to allow separate time steps for distinct conservation laws: one type of step conserves energy and the other conserves momentum (e.g., dipole alignment). This “orthogonal dynamics” explains how the relaxation of a single parameter can exhibit multiple responses such as primary, secondary, and microscopic peaks in the dielectric loss of supercooled liquids, and the crossover in thermal fluctuations from Johnson–Nyquist (white) noise at high frequencies to 1/f-like noise at low frequencies. Nanothermodynamics also provides new insight into three basic questions. First, it gives a novel solution to Gibbs’ paradox for the entropy of the semi-classical ideal gas. Second, it yields the stable equilibrium of Ising’s original model for finite-sized chains of interacting binary degrees of freedom (“spins”). Third, it confronts Loschmidt’s paradox for the arrow of time, showing that an intrinsically irreversible step is required for maximum entropy and the second law of thermodynamics, not only in the thermodynamic limit but also in systems as small as N=2 particles.

Members within and outside game design and game studies communities have critiqued the lack of diversity in the fields. Encouraging school-age children and youth from diverse backgrounds is one approach to addressing this concern. New Mexico State University’s (NMSU) Learning Games Lab has developed a Toolkit that enhances children and youth’s interests in being game developers, knowledge and skill in reviewing games and digital media, and engagement in the game design process. By using teaching and learning principles based in Universal Design for Learning, culturally responsive education, and media literacy, the Learning Games Lab creates learning experiences that cultivate a sense of belonging in game communities and foster critical thinking and creativity for children and youth of diverse backgrounds.

Accessible games are valued, doable and ultimately, accessible design is teachable. While the game community has been increasing its accessibility efforts, it can still feel challenging for design teams to prioritize and design for accessibility, particularly on games for learning. Some guidelines can be overwhelming and intimidating and may present contradictions when addressing different players’ needs. Learners need an opportunity to think through accessibility needs on a spectrum, consider categories (such as visual, hearing, motor and cognitive), and review designs in ways that are meaningful and doable. Designers and design students can learn accessibility design through a collaborative and participatory process. This established accessibility framework has been designed to help a facilitator guide participants through best practices on accessibility and apply it to the design process of transformational games. This collaborative learning leads to shared reflection on how to best teach accessibility and can be adjusted for use in formal classes or informal professional settings tailored based on the participants' needs.

The study was a comparison of general students of promise affect and mathematical students of promise affect after doing a mathematical modeling activity. Participants? gender (n=160), in grades 7-8, were nearly equal in number (81 girls & 79 boys). After completing a Model-eliciting Activity (MEA) in groups of three, participants completed the 31-item Chamberlin Affective Instrument for Mathematical Problem Solving, hereafter referred to as CAIMPS (Chamberlin, Moore, & Parks, 2017). Using four subconstructs, it was determined that the only statistically significant difference in student affect among the groups was self-esteem and self-efficacy (SS) with the general students of promise group having a mean of 3.43 and the mathematical students of promise group having a mean of 3.76. Implications are that the difference in SS may have surfaced because of the mathematical demands of the problems that ultimately influenced participants? ratings. Three subconstructs (Attitude Value Interest [AVI], Anxiety [ANX], and Aspiration [ASP]) may not have realized a statistically significant difference because they were not as contingent upon mathematical content knowledge as was SS. The final implication is that similar affective ratings may be an indication that MEAs are similarly suitable for use with groups containing individuals with varying talents.

Coronavirus (CoV) cause considerable morbidity and mortality in humans and other mammals, as evidenced by the emergence of Severe Acute Respiratory CoV (SARS-CoV) in 2003, Middle East Respiratory CoV (MERS-CoV) in 2012, and SARS-CoV-2 in 2019. Although poorly characterized, natural genetic variation in human and other mammals modulate virus pathogenesis, as reflected by the spectrum of clinical outcomes ranging from asymptomatic infections to lethal disease. Using multiple human epidemic and zoonotic Sarbecoviruses, coupled with murine Collaborative Cross genetic reference populations, we identify several dozen quantitative trait loci that regulate SARS-like group-2B CoV pathogenesis and replication. Under a Chr4 QTL, we deleted a candidate interferon stimulated gene, Trim14 which resulted in enhanced SARS-CoV titers and clinical disease, suggesting an antiviral role during infection. Importantly, about 60 % of the murine QTL encode susceptibility genes identified as priority candidates from human genome-wide association studies (GWAS) studies after SARS-CoV-2 infection, suggesting that similar selective forces have targeted analogous genes and pathways to regulate Sarbecovirus disease across diverse mammalian hosts. These studies provide an experimental platform in rodents to investigate the molecular-genetic mechanisms by which potential cross mammalian susceptibility loci and genes regulate type-specific and cross-SARS-like group 2B CoV replication, immunity, and pathogenesis in rodent models. Our study also provides a paradigm for identifying susceptibility loci for other highly heterogeneous and virulent viruses that sporadically emerge from zoonotic reservoirs to plague human and animal populations.

The geographical range of schistosomiasis is affected by the ecology of schistosome parasites and their obligate host snails, including their response to temperature. Previous models predicted schistosomiasis' thermal optimum at 21.7°C, which is not compatible with the temperature in sub-Saharan Africa (SSA) regions where schistosomiasis is hyperendemic. We performed an extensive literature search for empirical data on the effect of temperature on physiological and epidemiological parameters regulating the free-living stages of S. mansoni and S. haematobium and their obligate host snails, i.e., Biomphalaria spp. and Bulinus spp., respectively. We derived nonlinear thermal responses fitted on these data to parameterize a mechanistic, process-based model of schistosomiasis. We then re-cast the basic reproduction number and the prevalence of schistosome infection as functions of temperature. We found that the thermal optima for transmission of S. mansoni and S. haematobium range between 23.1-27.3°C and 23.6-27.9°C (95% CI) respectively. We also found that the thermal optimum shifts toward higher temperatures as the human water contact rate increases with temperature. Our findings align with an extensive dataset of schistosomiasis prevalence in SSA. The refined nonlinear thermal-response model developed here suggests a more suitable current climate and a greater risk of increased transmission with future warming for more than half of the schistosomiasis suitable regions with mean annual temperature below the thermal optimum.